The aims of the propose research are to investigate the mechanism of alcohol potentiation of halogenated hydrocarbon-induced hepatotoxicity, the mechanism of destruction of cytochrome P-450 by carbon tetrachloride, the effect of hypoxia on halogenated hydrocarbon-induced toxicity, and the synergistic toxicity of halogenated hydrocarbons. These studies will be conducted in rats, and carbon tetrachloride is the major chemical to be studied. The long-range goal is to understand the biochemical mechanisms by which halogenated hydrocarbons, an important group of environmental chemicals, produce cellular damage.